Journal of Diabetes最新文献_第4页

Sitagliptin, a DPP-4 Inhibitor, Effectively Promotes the Healing of Diabetic Foot Ulcer: A Randomized Controlled Trial 西格列汀，一种DPP-4抑制剂，有效促进糖尿病足溃疡愈合：一项随机对照试验

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-09-15 DOI: 10.1111/1753-0407.70156

Wei Gao, Dawei Chen, Hua He, Nenggang Jiang, Lihong Chen, Xingwu Ran

Background

This randomized controlled trial (RCT) was designed to evaluate the effects of sitagliptin on diabetic foot ulcers (DFUs).

Methods

This was a randomized, open-label clinical trial. The participants were assigned to either the control group, which received standard conventional therapy alone, or the sitagliptin treatment group, which received an oral administration of sitagliptin (100 mg once daily) in conjunction with standard conventional therapy. The primary endpoints were the ulcer healing rate and adverse reactions. The secondary endpoints included the time to ulcer healing, peripheral blood CD34+ endothelial progenitor cells (EPCs) count, serum levels of stromal cell-derived factor-1α (SDF-1α), and glycosylated hemoglobin A1c (HbA1c).

Results

A total of 62 subjects were enrolled in this trial, with 31 individuals assigned to each group. One participant from each group was lost to follow-up. Posttrial analysis revealed that, compared with the control group, the sitagliptin group demonstrated a significantly greater reduction in ulcer area and improved efficacy in terms of ulcer healing (p < 0.05). Although not statistically significant (p = 0.071), the sitagliptin group also tended to have a shorter ulcer healing time. Additionally, the sitagliptin group presented significantly greater numbers of CD34+ EPCs and higher SDF-1α levels compared to the control group (p < 0.05). No statistically significant difference in HbA1c levels was observed between the two groups (p > 0.05). No adverse events associated with sitagliptin treatment were reported.

Conclusions

The DPP-4 inhibitor sitagliptin may facilitate the healing of DFUs independent of its glucose-lowering effects, potentially by enhancing the mobilization of CD34 + EPCs in peripheral blood.

Trial Registration: Registration number: ChiCTR 2000029230, Approval date: 2020/01/19

本随机对照试验（RCT）旨在评估西格列汀对糖尿病足溃疡（DFUs）的影响。方法采用随机、开放标签临床试验。参与者被分为对照组和西格列汀治疗组，对照组单独接受标准常规治疗，西格列汀治疗组在标准常规治疗的同时口服西格列汀（100mg，每日一次）。主要终点为溃疡愈合率和不良反应。次要终点包括溃疡愈合时间、外周血CD34+内皮祖细胞（EPCs）计数、血清基质细胞衍生因子-1α (SDF-1α)水平和糖化血红蛋白A1c （HbA1c）。结果本试验共纳入62名受试者，每组31人。每组有一名参与者失去随访。试验后分析显示，与对照组相比，西格列汀组在溃疡面积缩小和溃疡愈合方面的疗效显著提高（p < 0.05）。虽然没有统计学意义（p = 0.071），但西格列汀组的溃疡愈合时间也更短。此外，与对照组相比，西格列汀组CD34+ EPCs数量和SDF-1α水平显著增加（p < 0.05）。两组患者HbA1c水平差异无统计学意义（p > 0.05）。未报告与西格列汀治疗相关的不良事件。结论DPP-4抑制剂西格列汀可能通过增强外周血CD34 + EPCs的动员而促进DFUs的愈合，而不依赖于其降血糖作用。试验注册：注册号：ChiCTR 2000029230，批准日期：2020/01/19

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引用次数: 0

The Contribution of Genetic Risk and Lifestyle Factors in the Progression of Diabetes to Diabetic Kidney Disease: A Prospective Cohort Study 遗传风险和生活方式因素在糖尿病发展为糖尿病肾病中的作用：一项前瞻性队列研究

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-09-10 DOI: 10.1111/1753-0407.70141

Yujiao Wang, Chunyang Li, Nongbu Cili, Jing Chen, Huazhen Yang, Ping Fu, Xiaoxi Zeng

Aims

Diabetes is a global public health crisis, especially when it is accompanied by microvascular complications such as diabetic kidney disease (DKD). The purpose of this study was to explore the relationship between the combined lifestyle factors of diabetes patients and their joint effects with genetic risk and the risk of DKD.

Materials and Methods

We included individuals diagnosed with diabetes at baseline from UK Biobank. Their lifestyle information was collected through a baseline questionnaire. Favorable lifestyle scores were constructed based on 5 common lifestyle factors and categorized into three levels. Genetic susceptibility to CKD was estimated by polygenic risk scores and further categorized into high, and low genetic risk categories. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations.

Results

By the end of follow-up, 1335 of 11 981 diabetes patients progressed to diabetes nephropathy. The COX regression results indicate that BMI ≥ 25 mg/m² and current or past smoking were risk factors for DKD, while alcohol consumption and moderate to high-intensity pysical exercise were protective factors. High genetic risk is significantly associated with increased risk of DKD (HR1.29, 95% CI 1.13–1.47, p < 0.001), while a favorable lifestyle had a protective effect (HR0.47, 95% CI 0.37–0.59, p < 0.001). Interaction analysis shows that there was neither additive nor multiplicative interaction between genetic risk and lifestyle.

Conclusions

Lifestyle factors and genetics are independently associated with susceptibility to incident DKD. A healthy lifestyle may attenuate elevated DKD risks due to genetic vulnerability.

目的：糖尿病是一个全球性的公共卫生危机，特别是当它伴有微血管并发症，如糖尿病肾病（DKD）时。本研究旨在探讨糖尿病患者的综合生活方式因素及其与遗传风险和DKD风险的共同作用之间的关系。材料和方法：我们纳入了来自UK Biobank的基线诊断为糖尿病的个体。他们的生活方式信息是通过基线问卷收集的。根据5个常见的生活方式因素构建良好的生活方式评分，分为3个等级。通过多基因风险评分来评估CKD的遗传易感性，并进一步分为高遗传风险和低遗传风险类别。采用Cox比例风险回归模型估计其相关性的风险比（HR）和95%置信区间（CI）。结果：随访结束时，11,981例糖尿病患者中有1335例进展为糖尿病肾病。COX回归结果显示，BMI≥25 mg/m2和当前或过去吸烟是DKD的危险因素，而饮酒和中高强度体育锻炼是DKD的保护因素。高遗传风险与DKD风险增加显著相关（HR1.29, 95% CI 1.13-1.47, p）。结论：生活方式因素和遗传与DKD易感性独立相关。健康的生活方式可以降低由于遗传易感性而增加的DKD风险。

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引用次数: 0

Diabetic Kidney Disease Update 糖尿病肾病最新进展

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-09-05 DOI: 10.1111/1753-0407.70150

Christian Mende, Zachary Bloomgarden

<p>The major determinants of the development of chronic kidney disease (CKD) in people with diabetes are hyperglycemia, hypertension, genetic susceptibility, dyslipidemia, and inflammation. By better understanding these factors, we can modify the risk of kidney damage and subsequent complications among people with diabetes. Elevation in glucose levels leads to both metabolic and hemodynamic changes, including glomerular hyperfiltration, podocyte injury, and progressive albuminuria, while hypertension accelerates glomerular damage [<span>1</span>]. Genetic predisposition, along with lifestyle factors such as obesity and smoking, further increases the risk. Dyslipidemia and oxidative stress contribute to endothelial dysfunction and tubulointerstitial injury [<span>2</span>], and inflammation [<span>3</span>] and activation of fibrotic pathways play important roles in disease progression [<span>4, 5</span>].</p><p>CKD is defined operationally by estimated glomerular filtrate rate (eGFR) < 60 mL/min and urine albumin/creatinine ratio (UACR) ≥ 30 mg/g present for 90 days or longer. Diabetes is responsible for roughly one-quarter to one-half of all CKD cases, with the proportion varying by region, population demographics, and stage of kidney disease [<span>6-8</span>]. This underscores the critical importance of diabetes prevention and optimal management to reduce the global burden of CKD. Albuminuria with normal renal function and/or an eGFR < 60 mL/min is associated with considerable cardiovascular mortality and heart failure risk. This has been underappreciated compared to the risk of progression of CKD and ESKD. In diabetic CKD, the risk of cardiovascular death is twice as great with eGFR < 60 mL/min and four times as great with eGFR < 45 mL/min, compared to normal renal function [<span>9</span>]. Compared to no albuminuria, mortality and heart failure admissions are four- and five-fold more likely in the presence of albuminuria, even when the eGFR is normal [<span>10, 11</span>].</p><p>Pharmacologic therapy is the cornerstone of treatment of diabetic CKD, with improvement in outcome seen with Renin-Angiotensin-Aldosterone system (RAAS) blockade, including mineralocorticoid inhibitors (MRA), sodium glucose transporter (SGLT) 2 inhibitors, and glucagon-like peptide (GLP)-1 receptor agonists (RA); significant therapeutic benefits also have been shown with aggressive therapy of comorbidities (hypertension, obesity and dyslipidemia) [<span>12</span>]. However, lifestyle modifications (diet/weight management, physical activity, smoking) and genetic risk have not received as much attention in clinical practice [<span>13</span>]. In a Dutch observational study, only 2% of patients adhered to all recommended lifestyle recommendations [<span>14</span>].</p><p>Three publications in the current Journal of Diabetes evaluate the aspects of the effects of lifestyle, social factors, genetic risks, and comorbidities as risk factors for the progression

糖尿病患者慢性肾脏疾病（CKD）发展的主要决定因素是高血糖、高血压、遗传易感性、血脂异常和炎症。通过更好地了解这些因素，我们可以降低糖尿病患者肾脏损伤和随后并发症的风险。葡萄糖水平升高导致代谢和血流动力学改变，包括肾小球高滤过、足细胞损伤和进行性蛋白尿，而高血压则加速肾小球损伤[1]。遗传易感性，以及生活方式因素，如肥胖和吸烟，进一步增加了风险。血脂异常和氧化应激可导致内皮功能障碍和小管间质损伤[2]，炎症[3]和纤维化通路激活在疾病进展中起重要作用[4,5]。CKD是通过肾小球滤过率(eGFR)≥60 mL/min和尿白蛋白/肌酐比(UACR)≥30 mg/g持续90天或更长时间来定义的。糖尿病约占所有CKD病例的1 / 4至1 / 2，这一比例因地区、人口统计和肾脏疾病分期而异[6-8]。这强调了糖尿病预防和优化管理的重要性，以减少慢性肾病的全球负担。肾功能正常和/或eGFR≤60 mL/min的蛋白尿与心血管死亡率和心力衰竭风险相关。与CKD和ESKD进展的风险相比，这一点被低估了。在糖尿病性CKD中，eGFR为60 mL/min时心血管死亡风险是正常肾功能bb0的2倍，eGFR为45 mL/min时心血管死亡风险是正常肾功能bb0的4倍。与无蛋白尿患者相比，即使eGFR正常，有蛋白尿患者的死亡率和心力衰竭入院率是无蛋白尿患者的4到5倍[10,11]。药物治疗是糖尿病性CKD治疗的基础，肾素-血管紧张素-醛固酮系统（RAAS）阻断可改善预后，包括矿化皮质激素抑制剂（MRA）、葡萄糖转运蛋白钠（SGLT） 2抑制剂和胰高血糖素样肽(GLP)-1受体激动剂（RA）；积极治疗合并症（高血压、肥胖和血脂异常）bbb也显示出显著的治疗效果。然而，生活方式的改变（饮食/体重管理、体育活动、吸烟）和遗传风险在临床实践中并没有得到那么多的关注。在荷兰的一项观察性研究中，只有2%的患者遵守了所有推荐的生活方式。当前《糖尿病杂志》上的三篇出版物评估了生活方式、社会因素、遗传风险和合并症作为CKD进展和终末期肾病（ESKD）发展的危险因素的影响。Cui和他的同事使用了中国健康与退休纵向研究（CHARLS）的纵向数据，该研究从2011年到2020年追踪了93226名参与者，研究了与45岁及以上中国人自述糖尿病和肾脏疾病相关的社会决定因素和生活方式因素。作者发现，从2011年到2020年，这一数字增长了10倍，尤其是在男性中，2020年的增幅特别大，可能与COVID大流行的额外影响有关。他们列举了一些因素，包括城市地区的年龄增长和医疗保健机会减少，该国北部地区的CKD发病率最高。值得注意的是，从他们的分析来看，吸烟、缺乏运动和不良饮食等生活方式的选择是主要原因。建议包括紧急处理积极的生活方式因素和社会决定因素，作为降低糖尿病慢性肾病风险的关键需要。在第二项研究中，Wang和同事研究了英国生物银行的参与者，利用前瞻性数据比较了1335名进展为糖尿病肾病的糖尿病患者和10646名未进展为糖尿病肾病的糖尿病患者，以评估遗传风险和生活方式因素在糖尿病进展为糖尿病肾病中的共同作用。分析的生活方式因素包括BMI、吸烟状况、饮酒、自我报告的饮食和体育锻炼，而CKD的遗传易感性是基于先前验证的多基因风险评分。年龄、糖尿病病程较长、HbA1c升高和高血压与风险相关，教育程度和收入水平也较低；更有利的生活方式因素的好处在具有高遗传风险的参与者中尤其明显，这表明一种方法可能允许个体分层，最大可能从生活方式干预中获益[10]。Liu及其同事分析了三个糖尿病患者队列，以评估较高的循环酮水平是否可能与更好的肾脏预后相关。在国家健康与营养检查调查（NHANES）数据库中，1257名糖尿病患者患有CKD，根据两次24小时饮食回顾（基于脂肪和蛋白质摄入与总营养摄入的比例）计算出的饮食生酮比例显示，饮食生酮指数越低，患ESKD的可能性越大。在一项对346例糖尿病和活检证实的糖尿病肾病患者的纵向研究中，尿蛋白中位数为5.0 g/天，随着β-羟基丁酸（B-OHB）的增加，肾脏不良结局的可能性逐渐降低，B-OHB的最高四分位数为0.28-0.99 mM/L，在27个月的观察期间，肾脏疾病进展率仅为最低四分位数（> 0.08 mM/L）的一半多一点。最后，在孟德尔随机化研究中，与较高的3-羟基丁酸相关的遗传变异表明，B-OHB与血清胱抑素C和肌酐水平呈显著负相关。值得注意的是，SGLT2抑制剂的一贯作用是增加B-OHB，这一作用被假设有助于其保护作用bb0。从这三篇讨论的出版物中可以得出什么临床信息？生活方式干预的益处的流行病学证据符合2024年KDIGO CKD指南，在控制高血压（血压130/80 mmHg，如果耐受收缩压120）、血脂异常（LDL 70 mg/L）、肥胖（BMI≤27）和高血糖（HbAIC 7%）方面，减缓糖尿病性CKD。需要更多地关注饮食调整，如限制蛋白质，减少植物蛋白和盐的摄入量，鼓励定期锻炼，不吸烟，并将体力活动增加到至少150分钟/周。SGLT2抑制剂在增加酮水平方面的作用可能比一般认为的更重要，适当的饮食调整以安全实现这一目标而不引起酮症酸中毒可能是未来研究的目标。良好生活方式的逐渐改善与糖尿病CKD的减少相关的研究结果令人印象深刻，并加强了其重要性。最后，遗传因素在糖尿病性CKD中的作用开始被更好地理解，这方面的CKD预防研究应该得到鼓励。作者声明无利益冲突。

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引用次数: 0

Indobufen Versus Aspirin Plus Clopidogrel in Patients After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the OPTION Trial 糖尿病患者冠状动脉支架植入术后吲哚布芬与阿司匹林加氯吡格雷的对比：OPTION试验的事后分析

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-09-05 DOI: 10.1111/1753-0407.70152

Shujing Wu, Huajie Xu, Lili Xu, Huanyi Zhang, Kang Cheng, Xiaoyan Wang, Manhua Chen, Guangping Li, Jiangnan Huang, Jun Lan, Guanghe Wei, Xin Zhao, Zhiyong Qi, Juying Qian, Hongyi Wu, Junbo Ge, the OPTION investigators

Background

Despite increased risk of ischemic events in diabetes, the optimal anti-thrombotic strategy for secondary prevention has not been defined. We aimed to assess the efficacy and safety of optimal antiplatelet agents such as indobufen-based dual antiplatelet therapy (DAPT) in patients with diabetes after coronary stenting.

Methods

OPTION trial was a randomized, open-label, noninferiority, and multicentric study in China. Enrolled subjects were randomized 1:1 to indobufen-based DAPT or aspirin-based DAPT. This post hoc analysis from OPTION trial was performed by the presence of diabetes. The primary endpoint was a 1-year composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5 bleeding.

Results

Of 4551 OPTION patients, the primary endpoint occurred in 93/1570 patients with diabetes (5.92%), as compared to 148/2981 without diabetes (4.96%) (HR: 0.72, 95% CI: 0.47–1.08, and HR: 0.73, 95% CI: 0.53–1.01, respectively), without significant interaction between diabetes status and treatment effect (P_interaction = 0.935). The secondary efficacy endpoint was comparable between patients with (HR: 1.31, 95% CI: 0.60–2.84) and without diabetes (HR: 0.95, 95% CI: 0.51–1.76) (P_interaction = 0.526). Similarly, both subgroups derived similar benefits for the safety endpoint (HR, 0.56; 95% CI, 0.34–0.92 for subjects with diabetes vs. HR, 0.66; 95% CI, 0.45–0.98 for those without diabetes; P_interaction = 0.609).

Conclusions

In patients receiving DES implantation, indobufen-based DAPT might be considered as a reasonable alternative to aspirin-based DAPT in the secondary prevention for those with diabetes, especially in patients at high bleeding risk.

背景：尽管糖尿病患者缺血性事件的风险增加，但二级预防的最佳抗血栓策略尚未确定。我们的目的是评估最佳抗血小板药物，如以吲哚布芬为基础的双重抗血小板治疗（DAPT）对冠状动脉支架植入术后糖尿病患者的疗效和安全性。方法OPTION试验是一项随机、开放标签、非劣效性、多中心的中国研究。入组的受试者按1:1的比例随机分为基于吲哚布芬的DAPT组和基于阿司匹林的DAPT组。这项来自OPTION试验的事后分析是在糖尿病患者存在的情况下进行的。主要终点是心血管死亡、非致死性心肌梗死、缺血性卒中、明确或可能的支架血栓形成或出血学术研究联盟（BARC）标准2、3或5型出血的1年复合研究。结果在4551例OPTION患者中，主要终点发生在93/1570例糖尿病患者（5.92%），而148/2981例非糖尿病患者（4.96%）（HR: 0.72, 95% CI: 0.47-1.08, HR: 0.73, 95% CI: 0.53-1.01），糖尿病状态与治疗效果之间无显著交互作用（p交互作用= 0.935）。次要疗效终点在糖尿病患者（HR: 1.31, 95% CI: 0.60-2.84）和非糖尿病患者（HR: 0.95, 95% CI: 0.51-1.76）之间具有可比性（p - interaction = 0.526）。同样，两个亚组在安全性终点上也获得了相似的获益（糖尿病患者的风险比为0.56；95% CI为0.34-0.92；非糖尿病患者的风险比为0.66；95% CI为0.45-0.98；相互作用p = 0.609）。结论在接受DES植入的糖尿病患者中，以吲哚布芬为基础的DAPT可作为阿司匹林为基础的DAPT的合理替代方案，用于糖尿病患者的二级预防，特别是出血高危患者。

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引用次数: 0

Associations of Stressful Life Events With Diabetes Incidence in China: Insights From the China Kadoorie Biobank 中国压力生活事件与糖尿病发病率的关系：来自中国嘉道理生物库的见解

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-09-01 DOI: 10.1111/1753-0407.70149

Jing Qian, Huiying Cheng, Xuening Dai, Dianjianyi Sun, Pei Pei, Meng Wang, Yingjun Li

Background

Limited empirical evidence exists on the link between exposure to various stressful life events (SLEs) and the heightened risk of Diabetes Mellitus (DM) within the mainland Chinese population.

Methods

We conducted this prospective cohort study with 455,464 participants from the China Kadoorie Biobank (CKB); we examined associations between SLEs exposures and DM outcomes. We employed multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders.

Results

Over a median follow-up of 10.1 years, 14,218 DM cases were identified. A dose–response relationship was observed between the number of SLEs, personal-related events, and the risk of DM. The higher the number of SLEs experienced, the higher the risk of developing diabetes (HR = 1.06, 95% CI = 1.01–1.12); individuals who experienced personal-related events had a higher risk of developing DM (HR = 1.17, 95% CI = 1.01–1.36), and those who experienced marital separation/divorce had a 53% increased risk of DM (HR = 1.53, 95% CI = 1.12–2.09). Subgroup analyses revealed effect modifications based on birth cohort, sex, and area.

Conclusion

By exploring the association of multiple SLEs with the development of DM, we identified marital separation/divorce as a driver of increased DM risk.

背景在中国大陆人群中，暴露于各种应激性生活事件（SLEs）与糖尿病（DM）风险升高之间的联系存在有限的经验证据。方法：我们对来自中国嘉道理生物库（CKB）的455,464名参与者进行了前瞻性队列研究；我们研究了SLEs暴露与糖尿病结局之间的关系。我们采用多变量Cox比例风险模型来估计风险比（hr）和95%置信区间（ci），并对潜在混杂因素进行调整。结果在10.1年的中位随访中，共发现14218例糖尿病病例。SLEs次数、个人相关事件与糖尿病风险之间存在剂量-反应关系。经历SLEs次数越多，发生糖尿病的风险越高（HR = 1.06, 95% CI = 1.01-1.12）；经历过个人相关事件的人患糖尿病的风险更高（HR = 1.17, 95% CI = 1.01-1.36），经历过婚姻分居/离婚的人患糖尿病的风险增加53% （HR = 1.53, 95% CI = 1.12-2.09）。亚组分析显示基于出生队列、性别和地区的效果改变。结论：通过探索多重SLEs与糖尿病发展的关系，我们确定婚姻分居/离婚是糖尿病风险增加的驱动因素。

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引用次数: 0

Impact of GLP-1 Receptor Agonists on Suicide Behavior: A Meta-Analysis Based on Randomized Controlled Trials GLP-1受体激动剂对自杀行为的影响：基于随机对照试验的荟萃分析

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-08-31 DOI: 10.1111/1753-0407.70151

Jingqi Chen, Qiufeng Zhang, Qingping Wu, Xiaoming Zhang, Zhiyi Xiang, Sidong Zhu, Tianfu Dai, Yuexiu Si

Background

This meta-analysis aims to assess the association between exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the incidence of suicidal behavior in patients with type 2 diabetes mellitus (T2DM)/obesity.

Methods

A comprehensive search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov, was conducted from the inception of the databases. The risk ratio (RR) and 95% confidence intervals (95% CI) were calculated.

Results

This meta-analysis included data from 25 randomized controlled trials (RCTs). The results indicated no significant difference in the incidence of suicidal behavior between the GLP-1 RA exposure group and the control group (RR = 0.84, 95% CI: 0.54–1.32, p = 0.46, I² = 0%). Subgroup analysis showed no significant differences in the incidence of suicidal behavior among participants with T2DM (RR = 0.74), obesity (RR = 1.07), adolescents (RR = 0.91), and adults (RR = 0.84). Additionally, no significant differences were observed between the two groups in any type of suicidal behavior, including suicidal ideation (RR = 1.04), suicide attempts (RR = 0.68), depression-related suicides (RR = 0.65), and completed suicides (RR = 1.06). There were also no significant differences between the groups for any type of GLP-1 RA, including dulaglutide (RR = 0.46), exenatide (RR = 0.98), semaglutide (RR = 0.82), lixisenatide (RR = 1.25), and liraglutide (RR = 0.92). No significant differences were observed between the exposure group and control group according to different comparators, including placebo (RR = 0.91) and others (RR = 1.08). All subgroup analyses showed p-values greater than 0.05 (two-sided tests) and I² values of 0%.

Conclusion

Our findings suggest that there is no significant association between GLP-1 RA exposure and suicidal behaviors in patients with T2DM or obesity.

本荟萃分析旨在评估2型糖尿病(T2DM)/肥胖患者暴露于胰高血糖素样肽-1受体激动剂（GLP-1 RAs）与自杀行为发生率之间的关系。方法从数据库建立之初，对PubMed、Web of Science、Cochrane Library和ClinicalTrials.gov等电子数据库进行全面检索。计算风险比（RR）和95%置信区间（95% CI）。结果本荟萃分析纳入了25项随机对照试验（rct）的数据。结果显示，GLP-1 RA暴露组与对照组自杀行为发生率无显著差异（RR = 0.84, 95% CI: 0.54 ~ 1.32, p = 0.46, I2 = 0%）。亚组分析显示，T2DM （RR = 0.74）、肥胖（RR = 1.07）、青少年（RR = 0.91）和成人（RR = 0.84）的自杀行为发生率无显著差异。此外，两组在自杀意念（RR = 1.04）、自杀企图（RR = 0.68）、抑郁相关自杀（RR = 0.65）和自杀完成（RR = 1.06）等任何类型的自杀行为方面均无显著差异。各组间GLP-1 RA的差异无统计学意义，包括杜拉鲁肽（RR = 0.46）、艾塞那肽（RR = 0.98）、semaglutide （RR = 0.82）、利昔那肽（RR = 1.25）和利拉鲁肽（RR = 0.92）。不同比较物，包括安慰剂组（RR = 0.91）和其他比较物（RR = 1.08），暴露组与对照组之间无显著差异。所有亚组分析显示p值大于0.05（双侧检验），I2值为0%。结论我们的研究结果表明GLP-1 RA暴露与T2DM或肥胖患者的自杀行为之间没有显著相关性。

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引用次数: 0

Response to Commentary on “Sleep Phenotypes, Genetic Susceptibility, and Risk of Obesity in Patients With Type 2 Diabetes: A National Prospective Cohort Study” 对《2型糖尿病患者睡眠表型、遗传易感性和肥胖风险：一项全国前瞻性队列研究》评论的回应

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-08-23 DOI: 10.1111/1753-0407.70145

Lei Xi, Juan Shi, Ying Peng, Yifei Zhang, Yanan Cao, Weiqing Wang

We thank the authors for their insightful comments and for recognizing that our manuscript provides valuable details about behavioral and genetic factors affecting the risk of obesity in people with type 2 diabetes (T2D) [1].

Firstly, as mentioned in our article, there may be recall bias based on patient self-reported sleep duration, and objectively measuring habitual sleep duration using actigraphy can provide more reliable data. However, considering its simplicity, practicality, and correlation with instrument measurement results, patients' self-reported sleep duration is still internationally recognized and widely used in population-based studies [2, 3].

Secondly, the relationship between sleep, diabetes and obesity is really complex and challenging. As mentioned by the authors, most exploratory experiments on sleep are temporary, especially for sleep deprivation. There are interactions among sleep, diabetes and obesity that impact cardiovascular and metabolic health, just like the intertwined trio. To avoid the potential impact of sleep related diseases, we excluded patients who reported implausible values of sleep duration (i.e., < 3 or > 12 h/night), use of sleeping aids, or psychiatric medications at baseline. It should be pointed out that the above efforts cannot completely eliminate the potential impact of sleep disorders on our study results, and how to reduce their potential effects is also one of the key considerations in our future research. The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) are indeed effective tools.

As we mentioned in the article, we acknowledge that “although we have adjusted for several covariates, there are potential confounders that could influence the results, such as dietary habits, physical activity, socioeconomic biases, and glucose-lowering medications, which we did not include in this study, and further research is needed to strengthen our understanding of these complex associations”, when it comes to both clinical and genetic analysis. In addition, a more complex and precise polygenic risk score (PRS) model for body mass index (BMI) is also under consideration.

In conclusion, we thank the authors for the wise and valuable comments and suggestions. We hope these clarifications address the issues raised and we intend to use more complex and appropriate models to explore their associations in future research.

The authors declare no conflicts of interest.

我们感谢作者的深刻见解，并承认我们的论文提供了影响2型糖尿病（T2D）患者肥胖风险的行为和遗传因素的有价值的细节。首先，正如我们在文章中提到的，基于患者自我报告的睡眠时间可能存在回忆偏差，使用活动描记仪客观测量习惯性睡眠时间可以提供更可靠的数据。然而，考虑到患者自我报告睡眠时间的简单、实用以及与仪器测量结果的相关性，患者自我报告睡眠时间仍然是国际上公认的，并被广泛应用于基于人群的研究[2,3]。其次，睡眠、糖尿病和肥胖之间的关系非常复杂和具有挑战性。正如作者所提到的，大多数关于睡眠的探索性实验都是暂时的，尤其是对睡眠剥夺的实验。睡眠、糖尿病和肥胖之间存在相互作用，影响心血管和代谢健康，就像交织在一起的三重奏一样。为了避免睡眠相关疾病的潜在影响，我们排除了在基线时报告睡眠持续时间（即每晚3或12小时）、使用助眠剂或精神药物的患者。需要指出的是，上述努力并不能完全消除睡眠障碍对我们研究结果的潜在影响，如何降低其潜在影响也是我们未来研究的重点考虑之一。匹兹堡睡眠质量指数（PSQI）和爱普沃斯嗜睡量表（ESS）确实是有效的工具。正如我们在文章中提到的，我们承认“尽管我们已经调整了几个协变量，但仍有可能影响结果的潜在混杂因素，如饮食习惯、体育活动、社会经济偏见和降糖药物，我们没有将其纳入本研究，需要进一步的研究来加强我们对这些复杂关联的理解”，当涉及到临床和遗传分析时。此外，一种更为复杂和精确的体重指数（BMI）多基因风险评分（PRS）模型也在考虑之中。最后，我们感谢作者提出的明智而宝贵的意见和建议。我们希望这些澄清能解决所提出的问题，我们打算在未来的研究中使用更复杂和合适的模型来探索它们之间的联系。作者声明无利益冲突。

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引用次数: 0

An Update on GLP-1 Receptor Agonists GLP-1受体激动剂的最新进展

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-08-22 DOI: 10.1111/1753-0407.70147

Zachary Bloomgarden

The glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a class of medications primarily developed for the management of type 2 diabetes (T2D) and are increasingly being used for various other health effects. Here's a simplified overview of their history, effects, and future prospects:

Glucose-dependent insulinotropic polypeptide (GIP) and then GLP-1 were identified in the 1970s as peptides potentiating the insulin secretory response to nutrient ingestion. In the early 1980s, the proglucagon amino acid sequence and gene were mapped, leading to the recognition of the common derivation of GLP-1 and GLP-2, produced in the L-cells of the distal small intestine, while GIP is produced in the K-cells of the proximal small intestine. The first therapeutically used GLP-1RA was isolated as exendin-4 from the saliva of a venomous lizard, Heloderma suspectum (the “Gila monster”), in 1992, with initial preclinical studies reported in 1996; although FDA approval for its use in treatment of T2D as exenatide was not granted until 2005. The next GLP-1RA used therapeutically was liraglutide, receiving approval in 2010, with dulaglutide receiving approval in 2014, semaglutide approval in 2017, and tirzepatide (a combined agonist of GLP-1 and GIP) approval in 2022; FDA approvals of liraglutide, semaglutide, and tirzepatide for treatment of obesity were granted in 2014, 2021, and 2023, respectively.

Both the GLP-1 and GIP receptor agonists enhance insulin production when glucose levels are elevated. This physiological insulin-secretory effect contrasts with the action of the older sulfonylureas, which activate the ATP-sensitive potassium channels of the pancreatic beta cells, mimicking the cellular process that physiologically acts to link insulin production to the beta cell's energy state. The consequent increase in endogenous insulin production leads the GLP-1RAs to have glucose-lowering action comparable to that of daily treatment with basal insulin [1]; with weight loss rather than weight gain and with lower likelihood of hypoglycemia [2, 3].

In addition to their glycemic benefits, GLP-1RAs are associated with improvement in mortality and in CV and renal outcomes in clinical trials [4, 5], both in people having and not having T2D [6], as well as in real-world studies of people with T2D [7] and of people with obesity without T2D [8]. In a study from the US Veteran's Affairs hospitals with mean followup of nearly 4 years comparing more than 200 000 persons receiving GLP-1RA with more than 1.2 million receiving usual care, benefits of GLP-1RAs included reduction in risk of stroke, myocardial infarction, pulmonary embolism, phlebitis, heart failure, hepatic failure, chronic kidney disease, bacterial infections, postprocedural respiratory complications, aspiration pneumonitis, chronic obstructive pulmonary disease, pneumonia and respiratory failure, a

人们对GLP-1RAs与其他糖尿病药物，特别是SGLT2抑制剂联合使用的兴趣越来越大。这种组合似乎增强了心血管和肾脏健康，显示出与单独使用GLP-1RA的个体相比，心力衰竭和死亡率的风险更低。新兴研究表明，GLP-1RAs可能预防神经退行性疾病，包括阿尔茨海默病[15]和帕金森病[16]，并对认知功能[17]产生有益影响；尽管其中一些可能只是反映了与glp - 1ra相关的中风减少。代谢相关的脂肪性肝病影响全球约三分之二的T2D患者，其中三分之二患有脂肪性肝炎，多项研究显示GLP-1RA对糖尿病和非糖尿病患者的益处[18,19]。GLP-1RAs与阻塞性睡眠呼吸暂停患者呼吸暂停低通气指数的降低有关，替西肽在这方面似乎更有效。GLP-1RA配方的创新包括口服选择和针对GIP、胰高血糖素、胰胰肽以及GLP-1的双作用和三作用药物，用于葡萄糖和体重管理。新药和生物仿制药正在测试中。口服活性GLP-1RAs与肠外给药GLP-1RAs具有相似的代谢、减肥和cv保护作用，尽管效力较弱。类似于“他汀假说”，他汀类药物与其降胆固醇效果成正比，可以预防或治疗心血管疾病，我们似乎接近于确认“GLP-1RA假说”，即这类扩展的药物可以预防或治疗心血管疾病，在一定程度上与其降体重和降血糖效果成正比，并具有多种额外的益处。然而，我们在这些药物上的成功也导致了一个两难的局面：全世界有近2亿人患有T2D和高心血管疾病风险。我们如何确保这些有效但非常昂贵的药物能够由我们现在认识的所有患者负担得起？作者声明无利益冲突。

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引用次数: 0

Association Between Serum Advanced Glycation End Products and Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A 3-Year Longitudinal Cohort Study (2019–2022) 血清晚期糖基化终产物与心血管-肾-代谢（CKM）综合征的相关性：一项为期3年的纵向队列研究（2019-2022）

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-08-21 DOI: 10.1111/1753-0407.70137

Hui Zhao, Ze-wen Zhang, Tao Luo, Dilihumaer Aili, Wen-huan Ding, Yuan-yuan Li, Yuan-sheng Gu, Shulipan Aslibek, Jing-jing He, Wen-hui Yu, Run-ze Ma, Anaer Gaoshao, Ting-ting Qiao, Guo-zhen Zhang, Henry S. Lynn, Mu-long Du, Jiang-hong Dai

Background

Cardiovascular-kidney-metabolic (CKM) syndrome begins with obesity and glucose abnormalities, advancing to cardiovascular and kidney complications. This study investigates the relationship of advanced glycation end products (AGEs) with CKM syndrome staging and transition patterns.

Methods

This 3-year longitudinal study (2019–2022) of 1264 adults identified five CKM trajectory groups: Group 1 (stable low-risk, 6.7%, stage 0/1), Group 2 (fluctuating, 15.8%, stages 0/1–2), Group 3 (stable intermediate, 52.8%, stage 2), Group 4 (progressors, 8.9%, to stage 3/4), and Group 5 (stable high-risk, 15.8%, stage 3/4), from baseline distributions of stage 0 (1.6%), 1 (12.3%), 2 (71.0%), 3 (5.8%), and 4 (9.2%). Serum AGEs were quantified by UPLC-MS/MS.

Results

Higher AGEs levels showed significant associations with CKM severity, with each 1-SD increase corresponding to a 30% greater likelihood of advanced staging (95% CI:10%–54%). Quartile analysis revealed a dose–response relationship (Q2:1.66[1.15–2.41]; Q3:1.67[1.12–2.48]; Q4:1.92[1.31–2.81]). Longitudinally, the total AGEs score was significantly associated with CKM transition patterns from 2019 to 2022. The odds ratios (ORs) for Group 2, Group 3, Group 4, and Group 5 compared to Group 1 were 1.61 (1.06–2.45), 1.64 (1.11–2.41), 1.71 (1.07–2.73), and 2.03 (1.32–3.13), respectively.

Conclusions

These findings suggest that serum AGEs are linked to CKM severity and progression, potentially serving as biomarkers for CKM staging and targets for intervention.

心血管-肾脏代谢综合征（CKM）始于肥胖和血糖异常，发展为心血管和肾脏并发症。本研究探讨晚期糖基化终产物（AGEs）与CKM综合征分期和过渡模式的关系。方法这项为期3年（2019-2022）的1264名成年人的纵向研究确定了5个CKM轨迹组：组1（稳定低风险，6.7%，0/1期）、组2（波动，15.8%，0/1 - 2期）、组3（稳定中等，52.8%，2期）、组4（进展，8.9%，至3/4期）和组5（稳定高风险，15.8%，3/4期），从0期（1.6%）、1期（12.3%）、2期（71.0%）、3期（5.8%）和4期（9.2%）的基线分布。采用UPLC-MS/MS法测定血清AGEs。结果较高的AGEs水平与CKM严重程度显著相关，每增加1-SD，晚期的可能性增加30% （95% CI: 10%-54%）。四分位数分析显示剂量-反应关系（Q2:1.66[1.15-2.41]; q2:1.67[1.12-2.48]; q2:1.92[1.31-2.81]）。纵向上，AGEs总分与2019 - 2022年CKM转变模式显著相关。组2、组3、组4、组5与组1的比值比（or）分别为1.61（1.06-2.45）、1.64（1.11-2.41）、1.71（1.07-2.73）、2.03（1.32-3.13）。这些研究结果表明，血清AGEs与CKM的严重程度和进展有关，可能作为CKM分期和干预目标的生物标志物。

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引用次数: 0

Supplementing Inosine to Blood Collection Tubes Adds a Glycolytic Inhibitory Effect 向采血管补充肌苷增加糖酵解抑制作用

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-08-20 DOI: 10.1111/1753-0407.70144

Yukio Kume, Motohiro Ohkubo, Naru NaKatuka, Sayaka Aritake-Okada, Teruhiko Yoshida, Hideaki Isago, Makoto Kurano

<p>At present, sodium fluoride (NaF)-supplemented tubes are used as usual blood collection tubes that can measure glucose and glycated hemoglobin (HbA1c) simultaneously. However, blood collection with NaF tubes show a decrease in glucose levels at room temperature within 4 h after blood collection [<span>1</span>]. The American Diabetes Association (ADA) guidelines recommend immersion of blood samples collected with heparin-lithium (Hp-Li) in ice water within 30 min or the use of tubes containing NaF and citrate buffer (FC) [<span>2</span>]. However, immediate immersion in ice water is difficult in clinical practice and citric acid is difficult to dissolve and is not suitable for HbA1c measurements because of hemolysis. Therefore, we aimed to develop blood collection tubes that are easier for clinical use than FC tubes and minimize blood glucose decline, compared with NaF tubes.</p><p>We collected 2 mL of whole blood each tube. Immediately after blood collection, each tube was agitated on a mix rotator at 3000 rpm (1470 g) for 5 min and then stored under storage conditions until immediately before measurement. The aliquoted blood collection tubes were stored at room temperature (25°C) or refrigerated (4°C). Then, the aliquoted whole blood was plasma-separated by centrifugation immediately and 2, 4, 24, and 48 h after collection. Glucose was measured immediately after separation, as well as HbA1c.</p><p>Changes in blood glucose levels in the NaF, FI, and FC tubes are shown in Figure 1A–D. Blood glucose changes were significantly attenuated to a greater degree in FI tubes than in NaF tubes at 4°C and 25°C conditions 4 and 24 h after sampling, whereas the blood glucose-preserving abilities of FI tubes were significantly inferior to those of FC tubes, except the case when stored at 4°C for 4 h. Regarding the criteria required from ADA (within 6.1% of the baseline blood glucose levels), the storage of FI blood collection tubes at 4°C did not reduce blood glucose levels by > 6.1%, which is the criteria required from ADA, in any sample up to 48 h, whereas the storage of FI blood collection tubes at room temperature reduced blood glucose levels by > 6.1% in 1 of 10 cases after 24 h (Figure S2), which were much superior to the NF tubes (Figures S1 and S2).</p><p>In addition, the enzymatic and immunoassay methods showed a significant difference with a <i>p</i> value of 0.005 in FC blood tubes, whereas no significant difference was observed for the FI blood tubes (Figure 1E,E). Concordantly, no significant difference in hemolytic Hb levels was observed in the NaF and FI tubes, but not in FC tubes, compared with Hp-Li tubes (Figure S4).</p><p>Regarding the mechanism, although the detail mechanisms will be published somewhere else, the inhibitory effects on ATP and glucose uptake decline in erythrocytes were considered. We believe that inosine addition to the NaF blood collection tube would contribute to measuring the blood glucose levels exactly, witho

目前常用的采血管采用氟化钠（NaF）补充管，可同时测量血糖和糖化血红蛋白（HbA1c）。然而，NaF管采血显示，采血后4小时内，室温下血糖水平下降。美国糖尿病协会（ADA）指南建议用肝素-锂（Hp-Li）采集的血液样本在冰水中浸泡30分钟或使用含有NaF和柠檬酸缓冲液（FC）[2]的管。然而，在临床实践中，立即浸泡在冰水中是困难的，柠檬酸难以溶解，由于溶血，不适合用于HbA1c的测量。因此，我们的目标是开发比FC管更易于临床使用的采血管，与NaF管相比，将血糖下降降到最低。每管取全血2ml。采集血液后，立即将每根试管在混合旋转器上以3000 rpm （1470 g）搅拌5分钟，然后在储存条件下保存至立即测量前。引用的采血管保存于室温（25℃）或冷藏（4℃）。然后，立即和采集后2、4、24、48 h进行离心血浆分离。分离后立即测量葡萄糖和HbA1c。NaF、FI和FC管的血糖水平变化如图1A-D所示。在4°C和25°C条件下，采样后4和24 h， FI管的血糖变化明显比NaF管减弱的程度更大，而FI管的血糖保存能力明显不如FC管，但在4°C保存4小时的情况除外。有关标准要求ADA(在6.1%的基线血糖水平),存储FI血液采集管在4°C没有降低血糖水平在6.1%,这是艾达的标准要求,在任何样本48 h,而FI血液采集管的存储在室温下血糖水平减少了在24小时后10例1的6.1%(图S2),这是优于NF管(图S1和S2)。此外，酶法和免疫法在FC血管中差异显著，p值为0.005，而在FI血管中差异不显著（图1E，E）。同样，与Hp-Li管相比，NaF和FI管中溶血Hb水平无显著差异，而FC管中则无显著差异（图S4）。关于其作用机制，虽然详细的机制将在其他地方发表，但考虑了对红细胞ATP和葡萄糖摄取下降的抑制作用。我们认为，在NaF采血管中加入肌苷将有助于准确测量血糖水平，而不会干扰HbA1c的测量。M.K.设计了这项研究。M.K.监督了这项研究。y.k., m.o., n.n.和M.K.进行了这项研究。Y.K.写了手稿。S.A.-O。， t.y., h.i.和M.K.审阅了手稿草稿。所有作者都对本文的全部内容负责，并已同意提交。本研究经东京大学医学研究生院伦理委员会批准(批准号：2020063 ni)。健康参与者提供书面知情同意书。作者声明无利益冲突。

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引用次数: 0